Immunohistochemical analysis in a morphologic spectrum of urachal epithelial neoplasms: diagnostic implications and pitfalls.	The vast majority of urachal epithelial neoplasms are adenocarcinomas with several described morphologic subtypes that include both enteric and nonenteric histologies. Adenocarcinoma from several other primaries may mimic any of these urachal adenocarcinoma subtypes in the bladder or at distant sites. However, data regarding the immunohistochemical profile of urachal carcinoma are limited, let alone its correlation with the different histologic subtypes that may have implications in the differential diagnostic workup with their morphologic mimics. Herein, we performed an immunohistochemical analysis in a broad spectrum of 39 urachal epithelial neoplasms (34 adenocarcinomas, 1 urothelial carcinoma, and 4 noninvasive mucinous cystic tumors), 13 urachal remnants, and 6 secondary colonic adenocarcinomas of the bladder, using an antibody panel that included novel and traditional gastrointestinal tract-associated markers. Expression levels of p63, CK7, CK20, CDX2, nuclear β-catenin, claudin-18, and Reg IV in urachal adenocarcinoma were as follows: 3%, 50%, 100%, 85%, 6%, 53%, and 85%. In urachal adenocarcinoma subtypes, expression levels of CDX2, nuclear β-catenin, claudin-18, and Reg IV were as follows: mucinous (8/8, 0/8, 6/8, 8/8), enteric (10/11, 1/11, 3/11, 8/11), not otherwise specified (5/7, 0/7, 3/7, 5/7), and signet ring cell (4/6, 0/6, 4/6, 6/6) type. All urachal adenocarcinomas had membrano-cytoplasmic β-catenin staining and only 2 tumors had nuclear localization that were focal to moderate, in contrast to secondary colonic adenocarcinoma of the bladder, which mostly had both membrano-cytoplasmic and nuclear positivity. Claudin-18 positivity was observed only in frankly malignant tumors and not in noninvasive urachal tumors and urachal remnants. Reg IV expression seemed to be related to mucin production, which was often diffuse in mucinous and signet ring cell subtypes and focal in enteric subtype, with goblet cell-like reactivity similar to secondary colonic adenocarcinoma. p63 expression was present in urothelial urachal remnants (3/3) and contrasted with CDX2 expression seen in glandular (5/6) and mixed urothelial/glandular remnants (2/4). Thus, this study showed that CDX2 is expressed by urachal remnants of glandular type, noninvasive urachal mucinous cystic tumors and urachal adenocarcinomas, and can be diffuse in urachal adenocarcinomas, even without the classic enteric morphology. Nuclear localization of β-catenin can rarely occur in urachal adenocarcinoma; however, diffuse nuclear reactivity argues against its diagnosis. The novel gastrointestinal tract markers claudin-18 and Reg IV are both expressed in urachal adenocarcinoma, including in signet ring cell carcinoma, and thus refutes the suggested specificity for gastrointestinal tract signet ring cell carcinomas. An immunohistochemical panel that includes β-catenin and CK7 may have value in differentiating urachal adenocarcinoma of enteric morphology from colonic adenocarcinoma. Overall, this study suggests that the different morphologic presentations of urachal adenocarcinomas have a relatively similar or overlapping immunophenotype. Knowledge of the similarity in immunostaining to its different morphologic mimics may help avoid misdiagnosis in urachal adenocarcinoma.	bladder